본문 바로가기
KERD
논문KCI 등재

트레드밀 운동이 streptozotocin에 의해 유발된 당뇨 쥐의 망막 신경세포 사멸에 미치는 영향

Effect of Treadmill Exercise on Apoptosis in the Retinas of Streptozotocin-Induced Diabetic Rats.

0

조회

0

다운로드

0

인용

0

참고문헌

키워드

초록

본 연구는 당뇨를 유발한 흰쥐에서 트레드밀 운동이 망막 신경세포의 사멸에 억제 효과가 있는지를 실험 하였다. 본 연구에서 Sprague-Dawley계 흰쥐 28마리를 대조군, 운동군, 당뇨군, 당뇨운동군으로 분류하여 각 군당 7마리씩 배정하였다. 당뇨는 streptozotocin을 복강에 주사하여 유발하였다. 운동군은 분당 8 m의 속도로 하루 30분씩 주 5회, 총 12주 동안 트레드밀 운동을 실시하였다. 본 연구의 결과, 당뇨 유발 흰쥐의 망막에서 세포사멸 인자인 terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL)-양성 세포수 그리고 caspase-3, cytochrome c, Bax의 발현이 증가되었으며, 항 세포사멸 인자인 Bcl-2의 발현은 감소되었다. 트레드밀 운동은 TUNEL-양성 세포수 그리고 caspase-3, cytochrome c, Bax의 발현을 감소시켰으며, Bcl-2의 발현은 증가시켰다. 본 실험의 결과, 당뇨에 의한 망막의 세포사멸 증가에 트레드밀 운동이 억제 작용을 나타내었으며, 따라서 트레드밀 운동은 당뇨 환자들에서 후유증을 경감시키는데 효과적인 치료법임을 알 수 있었다.

Abstract

In the present study, we investigated the effect of treadmill exercise on apoptotic neuronal cell death in the retinas of streptozotocin-induced diabetic rats. Twenty-eight male Sprague-Dawley rats were used for this study. The animals were divided into four groups(n = 7 in each group):(1) control group, (2) exercise group, (3) diabetes-induced group, (4) diabetes-induced and exercise group. Diabetes mellitus(DM) was induced by intraperitoneal injection of streptozotocin. The rats in the exercise groups were forced to run on the treadmill for 30 minutes once a day, five times per a week, during 12 weeks. In this study, a terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL) assay and western blot for the expressions of caspase-3, cytochrome c, Bax, and Bcl-2 in the retinas were conducted for the detection of apoptotic retinal cell death. The present results showed that the number of TUNEL-positive cells was increased in the retinas of the diabetic rats, whereas treadmill exercise suppressed this number. The expressions of pro-apoptotic factors caspase-3, cytochrome c, and Bax were enhanced and the expressions of anti-apoptotic factor Bcl-2 was decreased in the retinas of the diabetic rats. In contrast, treadmill exercise suppressed the expressions of caspase-3, cytochrome c, and Bax and increased the expression of Bcl-2. The present study demonstrated that treadmill exercise suppressed diabetes-induced apoptotic neuronal cell death in the retinas. Based on the present results, treadmill exercise may be effective therapeutic strategy for the alleviating complications of diabetes patients.

참고문헌 (57)

  1. 김기정, "지구성 트레드밀 운동이 모체감염으로 유발된 뇌성마비 쥐의 운동기능, 정서기능 및 인지기능에 미치는 영향", 운동과학, 18(3), pp.401~408 (2009), 한국운동생리학회
  2. 김영표, "지구성 운동강도 차이가 streptozotocin 유발 당뇨쥐의 인슐린 및 골격근 제4형 당수송체(GLUT-4) 발현에 미치는 영향", 운동과학, 13(2), pp.211~222 (2004), 한국운동생리학회
  3. 백성수, "자발적 휠 달리기를 포함한 enriched 환경이 streptozotocin에 의해 유발된 당뇨 쥐 해마의 신경세포생성과 단기기억력에 미치는 효과", 운동과학, 15(3), pp.259~268 (2006), 한국운동생리학회
  4. 이희혁, "트레드밀 운동이 streptozotocin로 유발된 당뇨쥐 췌장과 신장조직의 항산화 효소와 형태학적 변화에 미치는 영향", 운동과학, 12(3), pp.467~482 (2003), 한국운동생리학회
  5. 조한샘, "트레드밀 운동이 6-OHDA로 유발된 파킨슨병 흰쥐 흑색질 내 염증지표에 미치는 영향", 운동과학, 21(1), pp.51~58 (2012), 한국운동생리학회
  6. Abu-El-Asrar, A. M., "Expression of apoptosis makers in the retinas of human subjects with diabetes", Invest. Ophthalmol. Vis. Sci, 45, pp.2760~2766 (2004)
  7. ACSM., "ACSM Guidelines for exercise testing and prescription. 8th ed" (2009), Lippincott Williams and Wilkins
  8. Adams, J. M., "The bcl-2 protein family: arbiters of cell survival", Science, 281, pp.1322~1326 (1998)
  9. Aiello, L. P., "Systemic considerations in the management of diabetic retinopathy", Am. J. Ophthalmol, 132, pp.760~776 (2001)
  10. Ames A 3rd., "Energy requirements of CNS cells as related to their function and to their vulnerability to ischemia:a commentary based on studies on retina", Can. J. Physiol. Pharmacol, 70, pp.158~164 (1992)
  11. Antonsson, B., "Bax is present as a high molecular weight oligomer", complex in the mitochondrial membrane of apoptotic cells, 2001, pp.276, 11615~11623
  12. Barber, A. J., "Neural apoptosis in the retina during experimental and human diabetes. Early onset and effect of insulin", J. Clin. Invest, 102, pp.783~791 (1998)
  13. Barber, A. J., "The Ins2Akita mouse as a model of early retinal complications in diabetes", Invest. Ophthamol. Visual. Sci, 46, pp.2210~2218 (2005)
  14. Behl, Y., "Diabetes enhanced tumor necrosis factor-alpha production promotes apoptosis and the loss of retinal microvascular cells in type 1 and type 2 models of diabetic retinopathy", Am. J. Pathol., 172, pp.1411~1418 (2008)
  15. Bhat, N. R., "Hydrogen peroxide activation of multiple mitogen-activated protein kinase in an oligodendrocyte cell line:role of extracellular signalregulated kinase in hydrogen peroxide-induced cell death", J. Neurochem, 72, pp.112~119 (1999)
  16. Busik, J. V., "Hyperglycemia -induced reactive oxygen species toxicity to endothelial cells is dependent on paracrine mediators", Diabetes, 57, pp.1952~1965 (2008)
  17. Cenni, M. C., "Long-term survival of retinal ganglion cells following optic nerve section in adult bcl-2 transgenic mice", Eur. J. Neurosci, 8, pp.1735~1745 (1996)
  18. Cheung, A. K, "Aldose reductase deficiency prevents diabetesinduced blood–retinal barrier breakdown, apoptosis, and glial reactivation in the retina of db", db mice, 2005, pp.54, 3119~3125
  19. David, A. A., "High glucose-induced oxidative stress causes apoptosis in proximal tubular epithelial cells and is mediated by multiple caspases", FASEB. J., 17, pp.908~910 (2003)
  20. Davidson, C. M., "Chronic cerebral hypoperfusion:loss of pupillary reflex, visual impairment and retinal neurodegeneration", Brain Res, 859, pp.96~103 (2000)
  21. Du, Y., "Hyperglycemia increases mitochondrial superoxide in retina and retinal cells", Free Radic. Biol. Med, 35, pp.1491~1499 (2003)
  22. Enari, M., "Caspase-activated DNase that degrades DNA during apoptosis, and its inhibitor ICAD", Nature, 391, pp.43~50 (1998)
  23. Fadeel, B., "All along the watchtower:on the regulation of apoptosis regulators", FASEB. J., 13, pp.1647~1657 (1999)
  24. Feigl, B., "Experimental hypoxia in human eyes:Implications for ischaemic disease", Clin. Neurophysiol, 118, pp.887~895 (2007)
  25. Feng, H. M., "Glucose-induced apoptosis in Human endothelial cells is mediated by sequential activations of c-Jun NH2-terminal kinase and Caspase-3", Circulation, 101, pp.2618~2624 (2000)
  26. Giannini, C., "Physical exercise and diabetes during childhood", Acta. Biomed, 1, pp.18~25 (2006)
  27. Gross, A., "BCL-2 family members and the mitochondria in apoptosis", Gen. Dev, 13, pp.1899~1911 (1999)
  28. Isenmann, S., "Bax antisense oligonucleotides reduce axotomy-induced retinal ganglion cell death in vivo by reduction of Bax protein expression", Cell. Death. Differ., 6, pp.673~682 (1999)
  29. Kerr, J. F., "Apoptosis:a basic biological phenomenon with-wide ranging implications in tissue kinetics", Bri. J. Cancer, 26, pp.239~257 (1972)
  30. Kidd, V. J., "Proteolytic activities that mediate apoptosis", Ann. Rev. Physiol., 60, pp.533~573 (1998)
  31. Kim, Y. P., "Magnitude and time-dependence of the effect of treadmill exercise on cell proliferation in the dentate gyrus of rats", Int. J. Sports Med, 24, pp.114~117 (2003)
  32. Kluck, R. M., "The release of cytochrome c from mitochondri a:a primary site for bcl-2 regulation of apoptosis", Science, 275, pp.1132~1136 (1997)
  33. Kothakota, S., "Caspase- 3-generated fragment of gelsolin:effector of morphological change in apoptosis", Science, 278, pp.294~298 (1997)
  34. Kowluru, R. A., "Diabetes-induced mitochondrial dysfunction in the retina. Invest", Ophthalmol. Vis. Sci, 44, pp.5327~5334 (2003)
  35. Kowluru, R. A., "Diabetes-induced activation of caspase-3 in retina:effect of antioxidant therapy", Free Radic. Res, 36, pp.993~999 (2002)
  36. Krady, J. K., "Minocycline reduces proinflammatory cytokine expression, microglial activation, and caspase-3 activation in a rodent model of diabetic retinopathy", Diabetes, 54, pp.1559~1565 (2005)
  37. Li, Y., "Bax-dependent and independent pathways of retinal ganglion cell death induced by different damaging stimuli", Exp. Eye. Res, 71, pp.209~213 (2000)
  38. Longo, A., "Posture changes and subfoveal choroidal blood flow", Invest. Ophthalmol. Vis. Sci., 45, pp.546~551 (2004)
  39. Lorenzi, M., "Early cellular and molecular changes induced by diabetes in the retina", Diabetologia, 44, pp.791~804 (2001)
  40. Martin, P. M, "Death of retinal neurons in streptozotocin -induced diabetic mice", Invest. Ophthalmol. Visual. Sci, 45, pp.3330~3336 (2004)
  41. Martin. S. J., "Protease activation during apoptosis:death by a thousand cuts?", Cell, 82, pp.349~352 (1995)
  42. Martinou, J. C, "Overexpression of BCL-2 in transgenic mice protects neurons from naturally occurring cell death and experimental ischemia", Neuron, 13, pp.1017~1030 (1994)
  43. Mikhailov, V., "Bcl-2 prevents Bax oligomerization in the mitochondrial outer membrane", J. Biol. Chem, 276, pp.18361~18374 (2001)
  44. Mizutani, M., "Accelerated death of retinal microvascular cells in human and experimental diabetic retinopathy", J. Clin. Invest, 97, pp.2883~2890 (1996)
  45. Mohr, S., "Caspase activation in retinas of diabetic and galactosemic mice and diabetic patients", Diabetes, 51, pp.1172~1179 (2002)
  46. Nakamura, M., "Excessive hexosamines block the neuroprotective effect of insulin and induce apoptosis in retinal neurons", J. Biol. Chem, 276, pp.43748~43755 (2001)
  47. Okuno, T., "Ocular blood flow changes after dynamic exercise in humans", Eye, 20, pp.796~800 (2006)
  48. Oshitari, T., "Diabetes:a potential enhancer of retinal injury in rat retinas", Neurosci. Lett., 390, pp.25~30 (2005)
  49. Podesta, F., "Bax is increased in the retina of diabetic subjects and is associated with pericyte apoptosis in vivo and in vitro", Am. J. Pathol., 156, pp.1025~1032 (2000)
  50. Schwartzman, R. A., "Apoptosis:the biochemistry and molecular biology of programmed cell death", Endocr. Rev, 14, pp.133~151 (1993)
  51. Seigel, G. M., "Systemic IGF-I treatment inhibits cell death in diabetic rat retina", J. Diabetes Complications, 20, pp.196~204 (2006)
  52. Sun. W., "A selective aldose reductase inhibitor of a new structural class prevents or reverses early retinal abnormalities in experimental diabetic retinopathy", Diabetes, 55, pp.2757~2762 (2006)
  53. Tang, J., "Non-uniform distribution of lesions and biochemical abnormalities within the retina of diabetic humans", Curr. Eye. Res, 27, pp.7~13 (2003)
  54. Thompson, C. B., "Apoptosis in the pathogenesis and treatment of disease", Science, 267, pp.1456~1462 (1995)
  55. Wang, X., "The cellular response to oxidative stress:influences of mitogenactivated protein kinase signaling pathways on cell survival", Biochem. J, 333, pp.291~300 (1998)
  56. Yang, J., "Prevention of apoptosis by bcl-2:release of cytochrome c from mitochondria blocked", Science, 275, pp.1129~1132 (1997)
  57. Zeng, X. X., "Neuronal and microglial response in the retina of streptozotocin -induced diabetic rats", Vis. Neurosci, 17, pp.463~474 (2000)

관련 논문AI추천

이 간행물의 다른 논문 (9건)